GeroScience最新文献

{"title":"Assessing the gut microbiota composition in older adults: connections to physical activity and healthy ageing","authors":"Catarina Ramos, Daniele Magistro, Gemma E. Walton, Anya Whitham, Nicola Camp, Carlos Poveda, Glenn R. Gibson, John Hough, Will Kinnear, Kirsty Hunter","doi":"10.1007/s11357-025-01605-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01605-w","url":null,"abstract":"<p>The composition and functionality of the gut microbiota (GM) changes throughout the life course. As we move into older age, it starts to shift towards a less healthy one, which may lead to an imbalance in the GM community. Strategies that can reverse age-related dysbiosis are an important part of healthy aging. Little is known about the GM composition of older adults with different physical activity (PA) levels and whether it might contribute to healthy ageing. The aim of this study was to compare the GM composition of older adults with different PA levels and assess if it is associated with healthy ageing. 101 participants aged between 65–85 years undertook anthropometric measures, a 6-min walking test, wore an accelerometer for 7 days and provided a faecal sample. Faecal GM composition was analysed using 16S rRNA sequencing. We found that those who fulfilled the WHO/UK PA recommendations had higher relative abundance of several health-related bacteria such as <i>Lactobacillus, F. prausnitzii</i> and <i>Roseburia intestinalis</i> and lower abundance of disease-associated bacteria such as <i>D.piger</i> or Enterobacterales when compared to those who did not reach PA recommendations. These findings suggest that PA might improve the GM composition and has the potential to, at least partially, revert age-associated dysbiosis and promote healthy ageing.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"33 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic age acceleration and mortality risk prediction in US adults","authors":"Angelico Mendy, Tesfaye B. Mersha","doi":"10.1007/s11357-025-01604-x","DOIUrl":"https://doi.org/10.1007/s11357-025-01604-x","url":null,"abstract":"<p>Epigenetic clocks have emerged as novel measures of biological aging and potential predictors of mortality. We examined all-cause, cardiovascular, and cancer mortality prediction by epigenetic age acceleration (EAA) estimated using different epigenetic clocks. Among 2105 participants to the 1999–2002 National Health and Nutrition Examination Survey aged ≥ 50 years old and followed for mortality through 2019, we calculated EAAs from the residuals of nine epigenetic clocks regressed on chronological age. We assessed the association of EAAs and pace of aging with mortality adjusting for covariates. During 17.5 years of median follow-up, 998 deaths occurred, including 272 from cardiovascular disease and 209 from cancer. Overall mortality was most significantly predicted by Grim EAA (<i>P</i> &lt; 0.0001) followed by Hannum (<i>P</i> = 0.005), Pheno (<i>P</i> = 0.004), Horvath (<i>P</i> = 0.03), and Vidal-Bralo (<i>P</i> = 0.04) EAAs. Grim EAA predicted cardiovascular mortality (<i>P</i> &lt; 0.0001), whereas Hannum (<i>P</i> = 0.006), Horvath (<i>P</i> = 0.009), and Grim (<i>P</i> = 0.01) EAAs predicted cancer mortality. Overall mortality prediction differed by race/ethnicity between non-Hispanic White and White participants for Horvath (<i>P</i>_interaction = 0.048), Hannum (<i>P</i>_interaction = 0.01), and Grim (<i>P</i>_interaction = 0.04) EAAs. Hannum prediction of cancer mortality also differed between the two races/ethnicities (<i>P</i>_interaction = 0.007). Despite being predictive in non-Hispanic White participants, Horvath (<i>P</i> = 0.75), Hannum (<i>P</i> = 0.84), and Grim (<i>P</i> = 0.10) EAAs failed to predict overall mortality in Hispanic participants, and Hannum EAA was not associated with cancer mortality in Hispanic participants (<i>P</i> = 0.18). In a US representative sample, Horvath, Hannum, SkinBlood, Pheno, Vidal-Bralo, and Grim EAAs as well as pace of aging predict mortality. Howbeit, Horvath, Hannum, and Grim EAAs were less predictive in Hispanic participants.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"19 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-Monothiopomalidomide, a new immunomodulatory imide drug (IMiD), blunts inflammation and mitigates ischemic stroke in the rat","authors":"Kai-Yun Chen, Shih-Chang Hsueh, Pathik Parekh, Buyandelger Batsaikhan, David Tweedie, Weiming Luo, Chirag Patel, Yung-Hsiao Chiang, Nicholas Bambakidis, Barry J. Hoffer, Chi-Zong Huang, Seong-Jin Yu, Kuo-Jen Wu, Yun Wang, Eunji Hong, Dong Seok Kim, Nigel H. Greig","doi":"10.1007/s11357-025-01573-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01573-1","url":null,"abstract":"<p>An overactive neuroinflammatory response is often evident in the elderly and is a significant contributor to brain tissue damage following acute ischemic stroke. Such an inflammatory response is largely mediated by microglial cells and peripheral blood mononuclear cells (PBMCs). Classical anti-inflammatory agents have not proved clinically effective in mitigating the impact of ischemic stroke but have highlighted targets for new drug development, in particular excessive proinflammatory cytokine release. The immunomodulatory imide drug (IMiD) class has shown potential in reducing neuroinflammation and switching microglial phenotypic expression away from a proinflammatory to a regenerative anti-inflammatory one. 3-Monothiopomalidomide (3-MP), a new IMiD, has a brain/plasma concentration ratio of 0.5 to 0.6, an oral bioavailability of 38.5%, and a monophasic disappearance of half-life 3.2 h following oral administration. 3-MP pretreatment mitigates lipopolysaccharide (LPS)-induced inflammation in cellular human PBMCs and, in rat studies, 3-MP pretreatment lowers proinflammatory cytokine levels in the conditioned media and in plasma and the brain, respectively. Administered systemically to rats challenged with middle cerebral artery occlusion (MCAo) and reperfusion, 3-MP post-MCAo treatment reduced infarction volume; improved body asymmetry, a behavioral measure of stroke impact; and lowered inflammation. In summary, 3-MP exerted neuroprotective effects via anti-inflammatory actions against MCAo-induced ischemic injury and represents a therapeutic that warrants further investigation as a treatment for brain damage and related disorders associated with excessive inflammation.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro-gyms as a catalyst for healthy aging in university and healthcare settings: applications for the Semmelweis-EUniWell Workplace Health Promotion Model Program","authors":"Noémi Mózes, Dorottya Árva, David Major, Mónika Fekete, Norbert Dósa, Andrea Lehoczki, Péter Varga, Kata Pártos, Wei Yi Hung, Giorgia Giovannetti, Daniele Vignoli, Beatrix Busse, Mariann Moizs, Iveta Nagyova, Yongjie Yon, György Purebl, Béla Merkely, Róza Ádány, Vince Fazekas-Pongor, Zoltán Ungvári","doi":"10.1007/s11357-025-01595-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01595-9","url":null,"abstract":"<p>Europe is experiencing a significant demographic shift, with aging populations posing economic and social challenges due to increased healthcare costs and a higher prevalence of age-related diseases. Hungary, in particular, faces these challenges acutely due to higher morbidity and mortality rates from a range of chronic age-related diseases and behavioral risk factors. Addressing these issues requires innovative approaches to promote healthy aging. Semmelweis University, the largest healthcare provider and leading health sciences university in the region, is developing a comprehensive healthy aging program. A critical pillar of this program is the Semmelweis-EUniWell Workplace Health Promotion Model Program, a pioneering initiative aimed at tackling unhealthy aging within Hungary’s workforce by leveraging the workplace as a platform for health promotion. Central to this program’s goal of combating sedentary lifestyles—a significant contributor to age-related health issues—is the innovative use of micro-gyms and motivational interviewing. Micro-gyms, with their compact size and accessibility, provide convenient exercise opportunities, while motivational interviewing fosters intrinsic motivation and personalized counseling to encourage sustained physical activity. Through concerted efforts and innovative approaches, including the implementation of micro-gyms, the Semmelweis-EUniWell Workplace Health Promotion Model Program aims to set a benchmark for workplace health promotion, fostering a healthier and more resilient aging population in Hungary. This program not only enhances the well-being of employees at Semmelweis University and its EUniWell partner institutions but also catalyzes broader transformations in workplace health promotion and healthy aging nationwide.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"87 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salutary effects of transdermal curcumin on multiple indices of health span in rodent models of normal aging and hypertension","authors":"Kai Mao, Ruixuan Wang, Kateryna Karpoff, Daniel Kerr, Probal Banerjee, Joel M. Friedman, Derek M. Huffman","doi":"10.1007/s11357-025-01607-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01607-8","url":null,"abstract":"<p>Geroscience has helped to usher in a new and exciting era of aging drug development and evaluation of novel and repurposed agents, as well as natural compounds purported to target one or more aging hallmarks. Among the latter, curcumin has long been pursued as a promising strategy but has failed to provide convincing evidence in human trials. Oral intake is the typical route of administration tested for the vast majority of gerotherapeutic candidates, including curcumin, but efficacy is dependent upon good oral bioavailability and pharmacokinetics. However, unlike FDA-approved oral medications, many natural compounds, such as curcumin, have poor oral bioavailability, which may explain their limited success in translation. To overcome these inherent limitations, we tested a novel solvent-based formulation of concentrated curcumin (VASCEPTOR®), developed for effective skin penetration and delivery of high amounts of bioactive curcuminoids directly to the circulation on aging and age-related conditions. We demonstrate that short-term topical treatment (7.5 mg per dose) with VASCEPTOR® twice per week can improve both vascular health in a rat model of hypertension, while a late-life intervention in aged mice improves multiple indices of health span, including improved exercise tolerance, motor coordination, diastolic function (<i>p</i> &lt; 0.05), a reduction in frailty status (<i>p</i> &lt; 0.05) and expression of some age-related markers in tissues, particular heart and kidney. Thus, these data suggest that the therapeutic potential of curcumin can potentially be dramatically enhanced by topical delivery and, along with other promising candidates, should be prioritized for further development, testing and deployment to potentially target some manifestations of aging in humans.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"17 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans","authors":"Iman Man Hu, Ana Serna, Stacia Everts, Lale Güngördü, Bauke V. Schomakers, Ellen A. A. Nollen, Arwen W. Gao, Riekelt H. Houtkooper, Georges E. Janssens","doi":"10.1007/s11357-025-01599-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01599-5","url":null,"abstract":"<p>Aging is a major risk factor for disease, and developing effective pharmaceutical interventions to improve healthspan and promote longevity has become a high priority for society. One of the molecular pathways related to longevity in various model organisms revolves around lowering AKT1 levels. This prompted our in silico drug screen for small molecules capable of mimicking the transcriptional effects of <i>AKT1</i> knockdown. We found topoisomerase inhibitors as a top candidate longevity-drug class. Evaluating multiple compounds from this class in <i>C. elegans</i> revealed that the topoisomerase inhibitor amonafide has the greatest benefit on healthspan and lifespan. Intriguingly, the longevity effect of amonafide was not solely dependent on <i>DAF-16/FOXO</i>, the canonical pathway for lifespan extension via <i>AKT1</i> inhibition. We performed RNA-seq on amonafide-treated worms and revealed a more youthful transcriptional signature, including the activation of diverse molecular and cellular defense pathways. We found the mitochondrial unfolded protein response (UPR^mt) regulator <i>afts-1</i> to be crucial for both improved healthspan and extended lifespan upon amonafide treatment. Moreover, healthspan was partially dependent on the immune response transcription factor <i>zip-2</i> and the integrated stress response transcription factor <i>atf-4</i>. We further examined the potential of amonafide in age-related disease. Treating a <i>C. elegans</i> model for Parkinson’s disease with amonafide improved mobility. In conclusion, we identified amonafide as a novel geroprotector, which activates mitochondrial-, pathogen-, and xenobiotic-associated defense responses that—though more studies are needed—may serve as a candidate for Parkinson’s disease therapy.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"213 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic and phosphoproteomic signatures of aging mouse liver","authors":"Rodrigo Mohallem, Allison J. Schaser, Uma K. Aryal","doi":"10.1007/s11357-025-01601-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01601-0","url":null,"abstract":"<p>The liver is a metabolic powerhouse, crucial for regulating carbohydrates, fats, and protein metabolism. In this study, we conducted a comparative proteomic and phosphoproteomic analysis of aging mouse livers from young adults (3–4 months) and old (19–21 months) mice to identify age-related changes in liver proteins and phosphosites, which were linked to various metabolic pathways. In old mice, proteins associated with the “complement and coagulation cascade,” “age-rage signaling in diabetic complications,” and “biosynthesis of unsaturated fatty acids” were increased, while those linked to “oxidative phosphorylation,” “steroid hormone biosynthesis,” and “tryptophan metabolism” were decreased. Interestingly, aging was marked by a significant decrease in liver protein phosphorylation, with nearly 90% of significant phosphosites being downregulated. Pathway analysis of the downregulated phosphosites highlighted connections to “non-small cell lung cancer,” “lysine degradation,” “cell differentiation,” and “glycerophospholipid metabolism.” Decreased phosphorylation of several kinases that are linked to cell proliferation, particularly those in the MAPK signaling pathway, including Erk1, EGFR, RAF1, and BRAF was also observed highlighting their important role in the liver. This study identified an important relationship between proteins, phosphosites, and their connections to known as well as new pathways, expanding upon our current knowledge and providing a basis for future studies focused on age-related metabolic traits.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"33 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated abdominal aortic calcification scoring from vertebral fracture assessment images and fall-associated hospitalisations: the Manitoba Bone Mineral Density Registry","authors":"Marc Sim, Abadi K. Gebre, Jack Dalla Via, Siobhan Reid, Mohammad Jafari Jozani, Douglas Kimelman, Barret A. Monchka, Syed Zulqarnain Gilani, Zaid Ilyas, Cassandra Smith, David Suter, John T. Schousboe, Joshua R. Lewis, William D. Leslie","doi":"10.1007/s11357-025-01589-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01589-7","url":null,"abstract":"<p>Abdominal aortic calcification (AAC), a subclinical measure of cardiovascular disease (CVD) that can be assessed on vertebral fracture assessment (VFA) images during osteoporosis screening, is reported to be a falls risk factor. A limitation to incorporating AAC clinically is that its scoring requires trained experts and is time-consuming. We examined if our machine learning (ML) algorithm for AAC (ML-AAC24) is associated with a higher fall-associated hospitalisation risk in the Manitoba Bone Mineral Density (BMD) Registry. A total of 8565 individuals (94.0% female, age 75.7 ± 6.8 years) who had a BMD and VFA image from DXA between February 2010 and December 2017 were included. ML-AAC24 was categorised based on established categories (ML-AAC24 = low &lt; 2; moderate 2 to &lt; 6; high ≥ 6). Cox proportional hazards models assessed the relationship between ML-AAC24 categories and incident fall-associated hospitalisations obtained from linked health records (mean ± SD follow-up, 3.9 ± 2.2 years). Individuals with moderate (9.6%) and high ML-AAC24 (11.7%) had a greater proportion of fall-associated hospitalisations, compared to those with low ML-AAC24 (6.0%). In age and sex-adjusted models, compared to low ML-AAC24, moderate (HR 1.49, 95% CI 1.24–1.79) and high ML-AAC24 (HR 1.89, 95% CI 1.56–2.28) were associated with greater hazards for a fall-associated hospitalisation. Results were comparable (HR 1.37, 95% CI 1.13–1.65 and HR 1.60, 95% CI 1.31–1.95, respectively) after multivariable adjustment, including prior falls and CVD, as well as medication use. Integrating ML-AAC24 into bone density machine software to identify high risk individuals would opportunistically provide important information on fall and cardiovascular disease risk to clinicians for evaluation and intervention.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"56 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polypharmacy and its association with dementia, Parkinson’s disease, and mortality risk in UK adults: a multistate modeling approach","authors":"Jordan Weiss, May A. Beydoun, Michael F. Georgescu, Ana I. Maldonado, Hind A. Beydoun, Nicole Noren Hooten, Jack Tsai, Minkyo Song, Allen Nieva, Michele K. Evans, Alan B. Zonderman","doi":"10.1007/s11357-025-01586-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01586-w","url":null,"abstract":"<p>Polypharmacy is common among older adults and has been linked to adverse outcomes such as dementia, Parkinson’s disease (PD), and mortality. However, its influence on transitions between these health states remains understudied in large, population-based cohorts. Using data from 361,970 UK Biobank participants aged 50 and older with up to 15 years of follow-up, we examined the association between polypharmacy, defined as the use of five or more medications, and transitions between health states: healthy, dementia, PD, and mortality. Multistate parametric models, including Weibull regression, were employed to estimate these associations, adjusting for demographics, socioeconomic status, cardiovascular health, and comorbidities. Latent class analysis was used to identify specific medication combinations associated with health transitions. Polypharmacy was significantly associated with higher risks of transitioning from healthy to dementia (hazard ratio [HR], 1.15; 95% CI, 1.07–1.23) and from healthy to death (HR, 1.11; 95% CI, 1.08–1.09). Women exhibited better cardiovascular health but higher polypharmacy prevalence compared to men. Latent class analysis revealed that certain medication combinations, such as omega-3 fatty acids and multivitamins, were inversely associated with dementia and mortality, independent of polypharmacy status. These findings highlight the complex relationship between polypharmacy and health transitions in older adults. Careful medication management may mitigate risks associated with polypharmacy, particularly among individuals at risk for neurodegenerative diseases. Further research is warranted to investigate the potential protective effects of specific medication combinations on health outcomes.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"30 18 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term dietary allyl isothiocyanate, a TRPA1 agonist, ameliorates cardiac fibrosis and diastolic dysfunction in aged mice","authors":"Chunqi Qian, Zachary Fernandez, Seyed A. Sadeghi, Arman Fotouhi, Liangliang Sun, Donna H. Wang, Shuangtao Ma","doi":"10.1007/s11357-025-01603-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01603-y","url":null,"abstract":"<p>Transient receptor potential ankyrin 1 (TRPA1) is a sensory channel expressed in vagal afferent nerves that detect noxious stimuli. <i>Trpa1</i> knockout accelerates age-related cardiac fibrosis and dysfunction in mice. This study investigated whether TRPA1 activation with its selective agonist, allyl isothiocyanate (AITC), prevents cardiac aging. Male and female 18-month-old C57BL/6 J mice were randomized to receive either a control diet or a diet containing 15 mg of AITC per kilogram of food for 6 months. At 24 months, aged mice on the control diet exhibited increased left ventricular wall thickness but maintained similar left ventricular volume and preserved systolic function compared to 18-month-old middle-aged mice. Additionally, aged mice on a control diet developed restrictive-like cardiomyopathy, characterized by a pathologically elevated E/A ratio. AITC treatment significantly improved diastolic function by normalizing the E/A ratio (<i>P</i> &lt; 0.01) and shortening isovolumetric relaxation time (<i>P</i> &lt; 0.01), without affecting left ventricular wall thickness, volume, or systolic function. Electrocardiographic analysis demonstrated that AITC treatment significantly increased heart rate variability (<i>P</i> &lt; 0.01) and parasympathetic nervous system index (<i>P</i> &lt; 0.05), indicating enhanced vagal activity. Histological analyses revealed decreased cardiac fibrosis and collagen I/III deposition in AITC-treated mice (all <i>P</i> &lt; 0.01). Proteomics analysis demonstrated that differentially expressed proteins in myocardial tissue were mainly enriched in pathways of collagen metabolism, extracellular matrix-receptor interaction, and fatty acid metabolism. These findings suggest that long-term dietary AITC may improve vagal tone, reduce cardiac fibrosis, and enhance diastolic function in aged mice, potentially through TRPA1 activation. TRPA1 could be a promising therapeutic target for age-related diastolic dysfunction.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"5 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}